The route of US 395 in California is split into two segments, as the highway exits and reenters California via Nevada. The southern segment crosses the Mojave Desert and Owens Valley and passes east of the Sierra Nevada. The northern segment also follows the Sierra Nevada and crosses the Modoc Plateau.[2]

U.S. Route 395 begins in Hesperia at a partial interchange with Interstate 15 as it heads north. The road enters into Adelanto, on the western edge of Victorville. Victorville, founded by the Santa Fe Railroad to take advantage of water along the Mojave River, and for most of its history home to George Air Force Base,[9] was the second fastest growing city in the United States for July 2006 to July 2007.[10] Although US 395 was once a rural road passing to the side of these cities, with growth these cities are encroaching on the highway and changing the character from rural to suburban.

Between Mojave and its junction with Route 395, Route 14 follows the edge of the Sierra Nevada mountains. Formerly US 6 and US 395 ran concurrent from this junction north to Bishop. US 395 follows the valleys along the eastern edge of the Sierra as the mountains gradually increase in altitude until reaching their peak at over 14,000 feet (4,300 m) near Lone Pine.[2] After passing by three small lakes, Little Lake, North and South Haiwee Reservoirs, the highway enters the Owens Valley.

US 395 traverses the entire length of the Owens Valley, entering the valley near the former site of the Owens Lake. The valley, named for one of explorer John C. Fremont's guides, was primarily home to Timbisha and Paiutes before European settlement. Formerly a fertile lake and valley, Owens Lake and the southern portion of the valley are now dry. Water from the valley is channeled for use by the City of Los Angeles, via the Los Angeles Aqueduct, in what is commonly called the California Water Wars.[15]
Along the shores of Owens Lake, the highway passes by Cartago and Olancha. Just north of the lake is Lone Pine. Lone Pine is noted as an access for both the highest point in the contiguous United States, Mount Whitney, and the lowest point in North America, Death Valley. Both Mount Whitney and the mountains surrounding Death Valley are visible from US 395.[2] From Lone Pine to Bishop, the US 395 corridor loosely follows another abandoned rail line, the Carson and Colorado Railroad, although for most of this run the rail line runs on the eastern edge of the valley, while the road mostly runs on the west edge. The US 395 corridor from Lone Pine north to the Nevada state line is noted for a high concentration of natural hot springs leading to the area being known as the "hot springs jackpot".[16]

At the north end of the valley sits Bishop, the largest city in the Owens Valley. Bishop serves as a gateway for the recreation areas of the Sierra Nevada, including Mammoth Mountain. At the north end of Bishop is the former separation with, and current terminus of, U.S. Route 6, a 3,205-mile (5,158 km) route which can take motorists ultimately to Provincetown, Massachusetts on the east coast. This point is also where the route of US 395 departs from former rail corridors, with the former Carson and Colorado grade following the modern US 6 corridor towards Hawthorne and Tonopah, Nevada.[12]

The scenery changes dramatically past Bishop as the highway reaches the end of the valley and with a single ascent, gains over 3,000 feet (910 m) in elevation. From here to Gardnerville, the highway is routed across spur ranges of the Sierra Nevada mountains.[2]

US 395 scales the Sierra Nevada on a ridge between the canyons of the Owens River and Rock Creek. Sherwin Summit, at 7,000 feet (2,100 m), is the first of five mountain passes crossed by US 395 in the Sierra Nevada. The highway enters Mono County midway up the ascent, called the Sherwin Grade.[2]

Eight miles (13 kilometers) past the junction leading to Mammoth, the highway crests the second summit, Deadman Summit, at 8,036 feet (2,449 m). This summit separates the Owens River watershed from that of Mono Lake, a salt lake with approximately three times the concentration of salt as the Ocean.[19]

Just before arriving at Mono Lake, US 395 has a brief concurrency with SR 120; the two routes separate at the southern end of Lee Vining. At this junction US 395 is 12 miles (19 km) from Tioga Pass, along route 120, the highest paved through route in California, and the eastern boundary of Yosemite National Park.[2]

Visible for miles, the highway finally passes Mono Lake, squeezed between the lake and the Sierra crest. The next geographic feature is Conway Summit. At 8,138 feet (2,480 m) in altitude, this is the highest point along US 395, and the highest point along a U.S. Highway in California. This Summit also separates the Mono Lake watershed from that of the East Walker River.[2]

The fourth summit crossed by US 395 in California is Devil's Gate Pass, elevation 7,519 feet (2,292 m), which separates the East and West Walker Rivers. The winding descent from Devil's Gate follows the West Walker River, exiting near the towns of Walker and Coleville in the Antelope Valley, a few miles south of Topaz Lake which is on the California-Nevada State Line.

Topaz Lake is where US 395 leaves California, to serve the Reno and Carson City metropolitan areas. The highway runs for 87 miles (140 km) in Nevada.[21] While in Nevada, the highway crosses one more pass, Simee Dimeh Summit, before exiting the mountains.[22] The highway returns to follow the receding escarpment of the Sierra.[2]

The highway enters the state in a corner of Sierra County, entering Lassen County just 3 miles (4.8 km) later. A short segment in Lassen County is a freeway with one exit, SR 70 at the Hallelujah Junction. This exit is numbered 8, even though it resides hundreds of miles from the origin of the highway; the exit number instead uses the distance from the point of re-entry to California.[23] Though SR 70 does not directly serve any major cities, the highway is noted as an all-weather crossing of the Sierras. Just less than 5 miles (8.0 km) from Hallelujah Junction is Beckwourth Pass, the lowest pass in the Sierra, used by both SR 70 and the Feather River Route.[24] SR 70 was at one time numbered U.S. Route 40 Alternate, using US 395 from this junction south to Reno to connect with the mainline US 40 (now Interstate 80). Though driving route 70 and US 395 is a much longer route between Reno and Sacramento than mainline US 40 (130 miles (210 km) versus 226 miles (364 km)),[25][26] the alternate route was more likely to be open during winter storms than US 40, which crested the sierra at Donner Pass.

The Camino Sierra was a trail from Los Angeles to Lake Tahoe loosely paralleling modern State Route 14, US 395, and State Route 89. The trail was first believed to be used by Jedediah Smith in 1826. The trail was in common use by prospectors passing through the area because of the California gold rush and Comstock Lode. Though this area was not directly affected by the gold and silver rushes, the Owens Valley was more fertile than the areas around the strikes in Nevada. Farmers and ranchers raised cattle and other goods to trade with the mining boom towns nearby. The town of Bishop was established to trade goods with the mining town of Aurora.[28] By 1860, the Camino Sierra was an established trail appearing in maps and guides. After these mining rushes died down, the Camino Sierra saw a revival because of the construction of the Los Angeles Aqueduct beginning in 1908. The route was promoted for its scenic value by the Southern Pacific Railroad, as a side trip from its rail lines, as far back as 1912.[29] By 1918, the Camino Sierra had been included in the Automobile Blue Book, an early road atlas of the United States.[30]

Both the northern and southern segments of the US 395 corridor were used by railroads built in the 1880s branching from the First Transcontinental Railroad in Nevada. Both lines were intended to connect the main Southern Pacific Railroad line in Nevada with other lines, but were never completed.

As first commissioned in 1926, US 395 was a minor spur route of U.S. Route 195 connecting Spokane, Washington with Canada.[33] During the 1930s, US 395 was extended from Spokane to San Diego, over the Camino Sierra, using several existing state routes. The extension first appeared on the Official Nevada Highway map in 1935 and its Californian equivalent in 1936.[34][35] By 1937, US 6 had been extended to California, concurrent with US 395 between Bishop and Inyokern.[34]

The new southern terminus of US 395 was at Pacific Highway (former US 101) in San Diego. Traveling north, US 395 traversed much of the path of modern SR 163 and I-15 to Poway Road, where it routed to the east along much of today's Pomerado Road to Lake Hodges, with various realignments over the years. Portions of Pomerado Road today are signed "Historic US 395". At Lake Hodges the highway crossed a now-replaced bridge to Escondido.

Past Escondido the route passed through Fallbrook using portions of what is now SR 78 and SR 76 before returning to I-15 near Temecula.[36] This portion was straightened to the route of modern I-15, by 1960.[37] Past Temecula, the route followed SR 79, SR 74, I-215 and I-15 until reaching the modern terminus in Hesperia.[37] This part would also be straightened with the construction of what is now I-215. In 1969, the portion south of Hesperia was removed and assigned to other routes.[38]

Over time the road was paved, upgraded and straightened. Some parts are now built to freeway standards. Among the more notable upgrades, the Los Peñasquitos Creek Arch Bridge, along the portion of former US 395 now used by I-15, was built in 1949, and replaced in 1964, with a second span built in 1977.[39]

Except where prefixed with a letter, postmiles were measured on the road as it was in 1964, based on its original southern terminus in San Diego, and do not necessarily reflect current mileage. R reflects a realignment in the route since then, M indicates a second realignment, L refers an overlap due to a correction or change, and T indicates postmiles classified as temporary (for a full list of prefixes, see the list of postmile definitions).[1] Segments that remain unconstructed or have been relinquished to local control may be omitted. The numbers reset at county lines; the start and end postmiles in each county are given in the county column.